Multiple Developmental Defects in sox11a Mutant Zebrafish with Features of Coffin-Siris Syndrome

Shaoting Jia; Xingxing Wu; Yunya Wu; Xuefan Cui; Binbin Tao; Zuoyan Zhu; Wei Hu

doi:10.7150/ijbs.47510

Multiple Developmental Defects in sox11a Mutant Zebrafish with Features of Coffin-Siris Syndrome

Int J Biol Sci. 2020 Oct 3;16(15):3039-3049. doi: 10.7150/ijbs.47510. eCollection 2020.

Authors

Shaoting Jia^{1

2}, Xingxing Wu^{1

2}, Yunya Wu^{1

2}, Xuefan Cui^{1

2}, Binbin Tao^{1

2}, Zuoyan Zhu¹, Wei Hu^{1

3

2}

Affiliations

¹ State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
² University of Chinese Academy of Sciences, Beijing 100049, China.
³ Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China.

Abstract

A previous study suggested that human Coffin-Siris syndrome is related to the mutation of SOX11. Since the homozygous SOX11 mutant mice died soon after birth, no suitable model was available for the study of the pathogenic mechanism of Coffin-Siris syndrome. To solve this problem, we generated two viable homozygous zebrafish mutants, sox11a^m/m and sox11b^m/m . We found that the sox11a^m/m mutant possessed Coffin-Siris syndrome features. The sox11a^m/m mutants exhibited growth deficiency from 3.3 hpf embryos to adulthood. Furthermore, the sox11a^m/m mutant also displayed microcephaly, narrow pupillary distance, achondroplasia, and bone deformity in adults. Growth deficiency could be rescued by the injection of sox11a mRNA at the one-cell stage. In addition, the expression levels of genes related to cartilage and bone were downregulated in the sox11a^m/m mutant, indicating that sox11a mainly affected the growth and development of zebrafish by regulating the expression of genes related to skeletal development. Our results indicate that sox11a^m/m mutant zebrafish offered a potential model system to help with the search for pathogenic mechanisms of human Coffin-Siris syndrome.

Keywords: CRISPR/Cas9; Coffin-Siris; sox11; zebrafish.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Abnormalities, Multiple* / genetics
Animals
Face / abnormalities
Hand Deformities, Congenital* / genetics
Intellectual Disability
Mice
Micrognathism* / genetics
Neck / abnormalities
Zebrafish / genetics

Supplementary concepts

Coffin-Siris syndrome